The aim of the research in this proposal is to construct microenvironments (secondary coordination spheres) about metal ions to direct their chemistry. A bio-inspired approach is utilized that incorporates principles of molecular architecture found in the active sites of metalloproteins. New modular multidentate ligands have been developed that create rigid organic frameworks around coordinatively unsaturated metal ions. These ligands position hydrogen bond (H-bond) donating or accepting groups proximal to metal centers, forming specific microenvironments. We will investigate how H-bond frameworks regulate the structural and reactivity of metal complexes with terminal oxo ligands and bis(mu-oxo) motifs. A special aspect of this work is consideration of H-bonds in dioxygen and C-H bond activation by metal complexes. Long term goals of this research include developing structure-function relationships in metal-assisted oxidative catalysis. Metalloproteins perform chemical reactions that have yet to be achieved in synthetic systems. This chemical versatility follows at least in part from the ability of the proteins to regulate the reactivity of their metal centers by adjustments of their microenvironment. Thus the function and dysfunction of metalloproteins can be understood in the context of changes in their microenvironments. This type of analysis necessitates basic reactivity studies in which the effects of single components can be analyzed individually as described herein. The systems outlined in this proposal can control the molecular components that define the structure around the metal ion(s), thus permitting the development of complexes whose activity can be tailored to a particular function. The ability to fine-tune the molecular design of the external ligand-binding site is beneficial for constructing microenvironments about reactive species. This allows for the systematic study of structure function relationships that can lead to a fundamental understanding of chemical and biological processes.